Systems and methods for particle portal imaging

ABSTRACT

A particle portal imaging (PPI) system and method are provided that can be used to provide a “beam&#39;s eye view” of a patient&#39;s anatomy as a charged particle beam is delivered to a target region of the patient&#39;s body. The PPI system is capable of performing real-time image acquisition and in-situ dose monitoring using at least exit neutrons generated within the patient. The PPI system can perform charged particle treatment (PT) monitoring to monitor the particle beam being used for PT.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a U.S. National Phase application under 35 U.S.C. §371 of PCT international application PCT/US2019031623 filed on May 9,2019, which claims priority to, and the benefit of the filing date of,U.S. provisional application entitled, “Systems, Devices, and Methodsfor Imaging and Spectral Dosimetry using Exit Neutrons and Photons forPatients Undergoing Particle Beam Therapy,” Ser. No. 62/669,116, filedon May 9, 2018, both of which are incorporated by reference herein intheir entireties.

TECHNICAL FIELD

The present invention is generally related to charged particle therapy(PT), and more particularly, to methods and systems for particle portalimaging.

BACKGROUND

The fundamental goal in radiation therapy (RT) treatment planning,whether it be X-ray radiation therapy (XRT) or charged PT, is tomaximize the dose delivered to the tumor while minimizing the dosedelivered to the surrounding tissue. To fulfill this objective,intensity modulated radiation therapy (IMRT) is often utilized, in whichcomplex beam sequences are delivered to the patient to generatesophisticated dose distributions that precisely target the tumor volume.However, the steep dose gradients in IMRT increase the risk of dose tosurrounding organs from small shifts on the order of millimeters inpatient position. This enhances the need for accurate localization ofthe target volume using image guidance systems or image guided radiationtherapy (IGRT).

Charged PT methods such as proton therapy and heavy ion therapy (12C)hold the promise of significantly reduced toxicity to normal tissuewhile focusing the radiation on the tumor in a manner more precise thanphoton RT, even with advances made with 3-D conformal RT and IMRT.Charged PT offers a dosimetric advantage in improving the radiation doseto critical organs (e.g., heart, lung, and esophagus) as compared withIMRT using photons (high energy X-rays). With PT, however, real-timeimage guidance, which provides information on the position of the tumortarget within the beam aperture, is hindered by the finite range of thecharged particles, the very physical property that allows itstherapeutic advantage over megavoltage X-rays.

A need exists for a way to monitor the proton beam used in PT to ensurethat only intended targets are irradiated.

SUMMARY

The present disclosure is directed to a particle portal imaging (PPI)system and method. The PPI system comprises a charged particle beamsource and an imaging system. The charged particle beam source generatesa charged particle beam that is directed toward a target region of abody of a patient such that a spread out bragg peak (SOBP) is producedinside of the patient's body. The SOBP inside of the body produces atleast exit neutrons. The imaging system comprises a radiation imager anda processor. The radiation imager is positioned to receive at least aportion of the exit neutrons and to generate one or more radiographicimages from the exit neutrons. The processor is in communication withthe radiation imager to receive the radiographic image(s) and isconfigured to perform one or more image processing algorithms thatprocess the radiographic image(s) to obtain information about thepatient.

In accordance with one aspect, the radiation imager is configured toperform a preferential selection process that selects the exit neutronsthat are used to generate said one or more radiographic images based atleast in part on energy levels of the exit neutrons.

In accordance with one aspect, the radiation imager comprises aconverter, a mirror and an optical sensor. The converter receives atleast the exit neutrons and converts them into light propagating in afirst direction. The mirror receives the light propagating in the firstdirection and directs at least a portion of the received light in asecond direction that is at a non-zero-degree angle to the firstdirection. The optical sensor receives at least a portion of the lightpropagating in the second direction. The optical sensor comprises anarray of sensor elements, and each sensor element generates a respectiveelectrical signal based on an amount of the light received thereby. Eachradiographic image corresponds to a combination of the electricalsignals generated by the sensor elements at a given time instant.

In accordance with one aspect, the converter is a scintillator.

In accordance with one aspect, the mirror is a forty-five-degree mirror,and the second direction is at a forty-five-degree angle to the firstdirection.

In accordance with one aspect, the optical sensor is a charge coupleddevice (CCD) sensor.

In accordance with another aspect, the optical sensor is a complementarymetal oxide semiconductor (CMOS) sensor.

In accordance with one aspect, the radiation imager comprises a detectorthat receives the exit neutrons, forward momentum neutrons and/orphotons and converts them into one or more radiographic images.

In accordance with one aspect, the charged beam source is a proton beamsource that generates a proton beam.

In accordance with one aspect, the radiation imager generates a seriesof radiographic images, and each radiographic image of the series iscaptured at a different instant in time during the PT session. At leastone of the image processing algorithms performed by the processoranalyzes the radiographic images of the series to identify at least oneparticular feature that is present in each radiographic image of theseries and to determine whether a position of the particular feature haschanged over the different instants of time.

In accordance with one aspect, at least one image processing algorithmperformed by the processor analyzes the radiographic image(s) to verifya geometry of the charged particle beam at the target region during acharged particle treatment (PT) session.

In accordance with one aspect, at least one image processing algorithmperformed by the processor analyzes the radiographic image(s) todetermine a radiation dose of the charged particle beam delivered to thetarget region during a PT session.

In accordance with one aspect, at least one image processing algorithmperformed by the processor analyzes the radiographic image(s) todetermine a radiation dose of the charged particle beam delivered toareas adjacent to the target region during a PT session.

In accordance with one aspect, the radiation imager is moved relative tothe patient during the PT session to change an angle of the radiationimager relative to the charged particle beam, and a plurality oftwo-dimensional (2-D) radiographic images are captured by the radiationimager at different respective angles of the radiation imager relativeto the charged particle beam. At least one image processing algorithmperformed by the processor is a reconstruction algorithm that generatesone or more three-dimensional (3-D) radiographic images from the 2-Dradiographic images.

In accordance with one aspect, the charged particle beam comprises apencil beam that is scanned through layers of the body of the patientduring the PT session such that at least one 2-D radiographic image isgenerated by the radiation imager per scanned layer. An image processingalgorithm performed by the processor combines the 2-D radiographs forall of the scanned layers and uses a proton beam energy associated witheach scanned layer to generate a three-dimensional (3-D) radiographicimage of the target region.

In accordance with one aspect, one image processing algorithm performedby the processor determines, based on the 3-D radiographic image,whether or not actual delivery of the charged particle beam to thetarget region met constraints of a treatment plan for an intendeddelivery of the charged particle beam to the target region.

In accordance with one aspect, one image processing algorithm performedby the processor determines, based on the 3-D radiographic image,whether a radiation dose delivered by the charged particle beam to thetarget region met constraints of a treatment plan for an intendedradiation dose to be delivered during a PT session.

In accordance with one aspect, one image processing algorithm performedby the processor modifies, based on the 3-D radiographic image, atreatment plan associated with the patient.

The method for performing PPI comprises:

with a charged particle beam source of a PPI system, generating acharged particle beam and directing the charged particle beam toward atarget region of a body of a patient such that a spread out bragg peak(SOBP) is produced inside of the patient's body, the SOBP inside of thebody producing at least exit neutrons;

with a radiation imager of an imaging system of the PPI system,receiving at least a portion of the exit neutrons and generating one ormore radiographic images from said at least a portion of the exitneutrons; and

with a processor of the imaging system, receiving said one or moreradiographic images and performing one or more image processingalgorithms that process said one or more radiographic images to obtaininformation about the patient.

In accordance with one aspect of the method, the method furthercomprises: in the radiation imager, performing a preferential selectionprocess that selects the exit neutrons that are used to generate saidone or more radiographic images based at least in part on the energylevels of the exit neutrons.

These and other features and advantages of the inventive principles andconcepts will become apparent from the following description, drawingsand claims.

BRIEF DESCRIPTION OF THE DRAWINGS

Many aspects of the invention can be better understood with reference tothe following drawings. The components in the drawings are notnecessarily to scale, emphasis instead being placed upon clearlyillustrating the principles of the present invention. Moreover, in thedrawings, like reference numerals designate corresponding partsthroughout the several views.

FIG. 1 is a schematic diagram of the PPI system in accordance with arepresentative embodiment.

FIG. 2 is a block diagram of an imaging system of the PPI system shownin FIG. 1 in accordance with a representative embodiment.

FIG. 3 shows a schematic diagram of the imaging system of the PPI systemin accordance with a representative embodiment in which a tissueequivalent phantom is imaged.

FIG. 4 shows a front plan view of the tissue equivalent phantom shown inFIG. 3 comprising cylindrical dowels that extend through the tissueequivalent phantom shown in FIG. 3 and simulate tissues of differentorgans of a patient.

FIG. 5 shows the neutron image of the tissue equivalent phantom shown inFIG. 3 captured by the radiation imager of the imaging system shown inFIG. 3.

FIGS. 6A and 6B are graphs of neutron spectral distributions that weremeasured using a He-4 gas detector at different angular locationsrelative to a water equivalent phantom that was irradiated using a beamof protons with an average energy of 176 MeV; FIG. 6A shows the pulseshape discrimination (PSD) result taken with the He-4 gas detector at aPT facility; FIG. 6B shows the spectroscopic comparison of protontherapy data with other know neutron sources such as D-D, D-T andCf-252.

FIG. 7 is a flow diagram of the PPI method in accordance with arepresentative embodiment.

FIG. 8 is a flow diagram representing the PPI method in accordance withone representative embodiment in which the processor shown in FIG. 2performs a particular image processing algorithm to determine whetherthe position of the patient has changed during the PT session.

FIG. 9 is a flow diagram representing the PPI method in accordance withanother representative embodiment in which the processor shown in FIG. 2performs a particular image processing algorithm that verifies whetheror not the geometry of the charged particle beam at the target regionduring the PT session is in accordance with the treatment plan.

FIG. 10 is a flow diagram representing the PPI method in accordance withanother representative embodiment in which the processor shown in FIG. 2performs a particular image processing algorithm that analyzes one ormore radiographic images to determine the radiation dose of the chargedparticle beam delivered at the target region during the PT session.

FIG. 11 is a flow diagram representing the PPI method in accordance withanother representative embodiment in which the processor shown in FIG. 2performs a particular image processing algorithm that analyzes one ormore radiographic images to determine the radiation dose of the chargedparticle beam delivered to areas adjacent to the target region duringthe PT session.

FIG. 12 is a flow diagram representing the PPI method in accordance withanother representative embodiment in which the processor shown in FIG. 2performs a particular image processing algorithm that reconstructs a 3-Dradiographic image from a plurality of 2-D radiographic images capturedat different angular positions of the radiation imager.

FIG. 13 is a flow diagram representing the PPI method in accordance withanother representative embodiment in which the processor shown in FIG. 2performs a particular image processing algorithm that generates a 2-Dradiographic image for each layer of the target region while the chargedparticle beam is scanned layer by layer.

FIG. 14 is a flow diagram representing the PPI method in accordance withanother representative embodiment in which the processor shown in FIG. 2performs a particular image processing algorithm that determines, basedon the 3-D radiographic image, whether a radiation dose delivered by thecharged particle beam to the target region during the PT session metconstraints of a treatment plan for an intended radiation dose to bedelivered during the PT session.

FIG. 15 is a flow diagram representing the PPI method in accordance withanother representative embodiment in which the processor shown in FIG. 2performs a particular image processing algorithm that determines, basedon the 3-D radiographic image, whether a radiation dose delivered by thecharged particle beam to areas adjacent to the target region during thePT session met constraints of a treatment plan.

DETAILED DESCRIPTION

The present disclosure is directed to a particle portal imaging (PPI)system and method that can be used to provide a “beam's eye view” of apatient's anatomy as a charged particle beam is delivered to a targetregion of the patient's body. The PPI system can perform real-time imageacquisition and in-situ dose monitoring using at least exit neutronsgenerated within the patient. The PPI system can perform PT monitoringto monitor the particle beam being used for PT.

When a particle beam of high-energy ions, such as electrons, photons,protons, or heavy ions, is made incident on a target, sufficientsecondary (i.e., exit) neutrons are generated from which the PPI systemcan generate radiographic images of the patient based at least on theexit neutrons generated within the Spread-Out Bragg Peak (SOBP) insideof the irradiated body. Other types of secondary radiation may also begenerated, such as X-ray radiation, for example. The radiographic imagesgenerated using the secondary neutrons passing through the patient'sbody may be utilized for a variety of reasons, including to assess thedose to anatomical structures adjacent to the target region.

The PPI system, which delivers charged particle (e.g., proton) beamsusing passive scattering or active scanning (also known as pencil beamscanning or particle beam scanning (PBS)), may be used to generate asingle “summed” image from the entire duration of the treatment beam, orstreamed images during time intervals of the treatment beam. For passivescattering proton beams, 2-D radiographic images of the patient'sanatomy using exit neutrons and/or photons are generated. In the case of2-D radiographic images, they may also be taken in differentorientations to reconstruct 3-D images. For PBS, each energy layerassociated with the PBS beam delivery can be used to generate a 2-Dimage, and all the energy layers can then combined to generate a 3-Dimage of the region of the patient where the protons deposit energy andproduce neutrons and xrays. These PPI base images can be color images orgrayscale images similar to other scanning technologies, such as X-ray,ultra sound, gamma, etc.

The PPI system and method disclosed herein may also be used to determinethe length, height, width, and/or volume of the cancer and/or organswithin the patient. Additionally, the PPI system and method may be usedto determine other aspects of the patient undergoing PT. For example,the PPI system and method may be used to verify the dose delivered tothe tumor target and to identify and/or analyze additional features forclinical PT, as would be recognized by one of ordinary skill in the arthaving the benefit of this disclosure.

The imaging system of the PPI system includes a neutron and/or photonconverter, such as a scintillator (for example, 6LiF—ZnS), or a detector(for example NOVA Scientific neutron sensitive micro channel plate (MCP)glass doped with 10B or Gd) or any other technology that convertsneutrons/photons into signals. In embodiments in which the neutronand/or photon converter such as a scintillator is used, the converterconverts the photons and/or neutrons into light and an optical sensor ofthe imaging system, such as a charge coupled device (CCD) sensor orcomplementary metal oxide semiconductor (CMOS) sensor converts the lightinto either color or grayscale images. This is an indirect conversion ofneutrons and/or photons into color or grayscale images. In the casewhere a neutron and/or photon detector is used in the imaging system,the detector receives neutrons and/or photons and performs a directconversion of the neutron and/or photons into an image. The term“radiation imager,” as that term is used herein, is intended to denoteboth types of devices, i.e., devices that perform direct or indirectconversion of neutrons and/or photons into color or grayscale images. Acombination of a scintillator and a CCD sensor is an example of aradiation imager that performs indirect conversion, whereas a neutronradiation detector, such as a He-4 gas detector, is an example of aradiation imager that performs direct conversion.

The scintillator or detector may be used in conjunction with a CCD/CMOScamera system using a mirror or optical fibers to direct thescintillator output to a sensor outside the direct path of the exitradiation, or overlaid on a flat panel detector, whereby thescintillator is placed directly onto the photodiode matrix of the flatpanel system, for improved light collection efficiency to produce eithercolor or grayscale images. The radiation imager may be positioned at anydistance from the target and at any angle depending on the positioningof the patient. A shield can be placed between the imaging system andthe cyclotron or synchrotron to remove or minimize the photons so thatneutron images of the patient's anatomy are produced by the imagingsystem.

The PT source is typically a cyclotron or synchrotron, which is aparticle accelerator commonly used as a source for the charged particlebeam therapy. A cyclotron or synchrotron produces higher energyparticles such as protons or 12C. These higher energy particles, duringthe interaction with matter, can produce secondary particles such aslike neutrons, electrons, x-rays and gammas.

In accordance with a representative embodiment, the PPI system measuresthe spatio-spectral distribution of secondary neutrons generated invarious locations within the patient's anatomy and in the beamcollimators. By measuring the spatio-spectral distribution, one canachieve two highly important tasks. First, the unscattered neutronswould be what irradiate secondary organs significantly in the forwardbeam direction past the cancer irradiation target. Secondly, thescattered neutrons now have a new direction and energy indicating notonly where but how much energy was deposited in specific organs. Usingthese two distinct neutron flux distributions, one can obtainsignificant additional understanding of secondary neutron-induced cancerrisk.

Additionally, since the neutrons generated will be highly dependent notonly on what the characteristics of a specific PT facility is, but alsowhich type and where a specific cancer is located, this will allowsignificant improvements to be made in patient-by-patient impact andrisk, and potentially be used as guidance for particle portal imaging. Aneutron radiation detector, such as a He-4 gas detector, for example,may be used to measure the spatio-spectral distribution of the secondaryneutrons. Knowledge of the spectral distribution of the secondaryneutrons can be used to optimize the detector energy response. Knowledgeof the proton beam characteristics and the neutron and/or photon spectragenerated can be used to optimize the radiation imager, includingcomposition and thickness of the scintillator. For example, using theneutron energy spectra, one can choose the neutron absorbing materialfor scintillation and its optimal thickness. This knowledge can be usedto select materials for the scintillator that maximize light generationand collection, and to select scintillator material and imager geometrythat maximizes selection of those exit neutron and xrays that producebest image quality based on spatial resolution and image contrast.

This PPI system and method apply to both passive spreading, in which oneor more scatterers are used to produce a homogenous proton beam profilewhich is then incident on a compensator to generate a charged particlebeam (e.g., proton beam) with the desired dose distribution in apatient; and active scanning or active spreading, in which magneticfields are used to generate or “paint” the treatment volume, also knownas intensity modulated proton therapy (IMPT) (the proton analogue tophoton based intensity modulated radiation therapy (IMRT)), voxel byvoxel in each layer, and in successive contiguous layers. The protonbeam is incident to these contiguous layers.

In the following detailed description, for purposes of explanation andnot limitation, exemplary, or representative, embodiments disclosingspecific details are set forth in order to provide a thoroughunderstanding of inventive principles and concepts. However, it will beapparent to one of ordinary skill in the art having the benefit of thepresent disclosure that other embodiments according to the presentteachings that are not explicitly described or shown herein are withinthe scope of the appended claims. Moreover, descriptions of well-knownapparatuses and methods may be omitted so as not to obscure thedescription of the exemplary embodiments. Such methods and apparatusesare clearly within the scope of the present teachings, as will beunderstood by those of skill in the art. It should also be understoodthat the word “example,” as used herein, is intended to benon-exclusionary and non-limiting in nature.

The terminology used herein is for purposes of describing particularembodiments only and is not intended to be limiting. The defined termsare in addition to the technical, scientific, or ordinary meanings ofthe defined terms as commonly understood and accepted in the relevantcontext.

The terms “a,” “an” and “the” include both singular and pluralreferents, unless the context clearly dictates otherwise. Thus, forexample, “a device” includes one device and plural devices. The terms“substantial” or “substantially” mean to within acceptable limits ordegrees acceptable to those of skill in the art. For example, the term“substantially parallel to” means that a structure or device may not bemade perfectly parallel to some other structure or device due totolerances or imperfections in the process by which the structures ordevices are made. The term “approximately” means to within an acceptablelimit or amount to one of ordinary skill in the art. Relative terms,such as “over,” “above,” “below,” “top,” “bottom,” “upper” and “lower”may be used to describe the various elements' relationships to oneanother, as illustrated in the accompanying drawings. These relativeterms are intended to encompass different orientations of the deviceand/or elements in addition to the orientation depicted in the drawings.For example, if the device were inverted with respect to the view in thedrawings, an element described as “above” another element, for example,would now be below that element.

Relative terms may be used to describe the various elements'relationships to one another, as illustrated in the accompanyingdrawings. These relative terms are intended to encompass differentorientations of the device and/or elements in addition to theorientation depicted in the drawings.

The term “memory” or “memory device,” as those terms are used herein,are intended to denote a non-transitory computer-readable storage mediumthat is capable of storing computer instructions, or computer code, forexecution by one or more processors. References herein to “memory” or“memory device” should be interpreted as one or more memories or memorydevices. The memory may, for example, be multiple memories within thesame computer system. The memory may also be multiple memoriesdistributed amongst multiple computer systems or computing devices. Morespecific examples (a nonexhaustive list) of the computer-readablestorage medium would include the following: an electrical connection(electronic) having one or more wires, a portable computer diskette(magnetic), a random access memory (RAM) (electronic), a read-onlymemory (ROM) (electronic), an erasable programmable read-only memory(EPROM or Flash memory) (electronic), an optical fiber (optical), and aportable compact disc read-only memory (CDROM) (optical). Note that thecomputer-readable medium could even be paper or another suitable mediumupon which the program is printed, as the program can be electronicallycaptured, via for instance optical scanning of the paper or othermedium, then compiled, interpreted or otherwise processed in a suitablemanner if necessary, and then stored in a computer memory. In addition,the scope of the certain embodiments of the present invention includesembodying the functionality of the preferred embodiments of the presentinvention in logic embodied in hardware or software-configured mediums.

A “processor” or “processing device,” as those terms are used hereinencompass an electronic component that is able to execute a computerprogram or executable computer instructions. References herein to asystem comprising “a processor” or “a processing device” should beinterpreted as a system having one or more processors or processingcores. The processor may for instance be a multi-core processor. Aprocessor may also refer to a collection of processors within a singlecomputer system or distributed amongst multiple computer systems. Theterm “computer,” as that term is used herein, should be interpreted aspossibly referring to a single computer or computing device or to acollection or network of computers or computing devices, each comprisinga processor or processors. Instructions of a computer program can beperformed by a single computer or processor or by multiple processorsthat may be within the same computer or that may be distributed acrossmultiple computers.

FIG. 1 is a schematic diagram of the PPI system 100 in accordance with arepresentative embodiment. During a PT treatment session, a chargedparticle beam (e.g., a proton beam, an electron beam, a photon beam, aheavy ion beam, etc.) 102 from a charged particle beam source 101, suchas a cyclotron or synchrotron, for example, produces a spread out braggpeak (SOBP) inside of a patient 104 who is lying on a table 103. TheSOBP inside of the patient 104 produces forward momentum neutrons 105,also referred to herein as exit neutrons 105. These exit neutrons 105are then absorbed/collected by a radiation imager 106. For ease ofdiscussion, it will be assumed that the radiation imager 106 is ascintillator, but direct conversion detectors of the type describedabove may instead be used.

In accordance with this representative embodiment, the radiation imager106 is mounted on an arm 107 that can be rotated around the patient 104to produce neutron images of the patient's anatomy at different anglesin line with the charged particle beam 102. The arm 107 may be C-shaped,although it can have other shapes. The arm 107 is mechanically coupledto a stand 108, which will typically have wheels 109 to allow it to beeasily positioned and moved.

FIG. 2 shows a block diagram of an imaging system 120 of the PPI systemin accordance with a representative embodiment. The imaging system 120comprises the radiation imager 106 shown in FIG. 1, a processor 125 anda memory device 126. The radiation imager 106 produces neutron images ofthe anatomy of the patient 104 (FIG. 1). In accordance with thisrepresentative embodiment, the exit neutrons 105 are received on theopposite side of the patient 104 from the source (not shown) by anindirect converter 111. As mentioned above, the radiation imager 106 maybe a combination of an optical sensor (e.g., a CCD sensor) and aneutron-to-light converter, such as a scintillator, for example, thatperforms direct conversion of neutrons to images or it may be adetector, such as, for example, a NOVA Scientific neutron sensitive MCPor a He-4 gas detector that performs direct conversion of neutronsand/or photons into an image. For ease of discussion, it will be assumedthat the radiation imager 106 comprises a neutron-to-light converter(e.g., a scintillator) 111 and an optical sensor 114 that act togetherto convert neutrons and/or photons into color or grayscale images. Inaccordance with a representative embodiment, the size of thescintillator is 200 millimeters (mm)×200 mm, although the inventiveprinciples and concepts are not limited to the scintillator having anyparticular dimensions or configuration.

The converter 111 converts the exit neutrons 105 and/or photons intolight 117, which is reflected by a 45° tilted mirror 112 toward anoptical sensor 114. The reflected light is collected by the opticalsensor 114, which may be, for example, a CCD sensor, a CMOS sensor orany other suitable optical sensor. The optical sensor 114 comprises anarray of sensor elements, or pixels, each of which generates arespective electrical signal based on light received by the respectivesensor element. These electrical signals together comprise an image ofthe anatomy of the patient 104 undergoing the treatment. The opticalsensor 114 can be cooled with a cooling system (not shown) to reduce thenumber of isolated hot pixels. To maximize the amount of light that isreceived by the optical sensor 114, a lens 115 is typically disposed inbetween the optical sensor 114 and the mirror 112. This entire setup maybe enclosed in a light tight L-shaped box 116.

FIG. 3 shows a schematic diagram of the imaging system 130 of the PPIsystem in accordance with a representative embodiment in which a tissueequivalent phantom 131 is imaged. Like the imaging system 120 shown inFIG. 2, the imaging system 130 comprises the radiation imager 106, theprocessor 125 and the memory device 126. The tissue equivalent phantom131 is sandwiched between solid water phantoms 132 and 133. The solidwater phantoms 132, 133 are disposed in between the radiation imager 106and the charged particle beam snout 101 a of the charged particle beamsource 101 such that the forward scattered spallation neutrons will beincident on the converter 111 of the radiation imager 106.

FIG. 4 shows a front plan view of the tissue equivalent phantom 131,which comprises cylindrical dowels 142 that extend through the tissueequivalent phantom 131 and simulate tissues of different organs of apatient. Hydrogen rich matter such as water will moderate or slow downthe neutrons passing through it. Thus, the gray scale intensity of theneutron image will vary with the hydrogen content in each of the dowels142 of the phantom 131.

FIG. 5 shows the neutron image 150 of the tissue equivalent phantom 131captured by the radiation imager 106 of the imaging system 130 shown inFIG. 3. The radiation imager 106 acquired this neutron image of thephantom based on the charged particle beam source 101 producing a 10centimeter (cm)×10 cm beam of protons with average energy of 176 MeV.Although the image is a bit grainy, it does provide useful informationthat can be used to improve treatment. The neutron moderation effectthat determined the gray scale intensity of the neutron image 150 mapsto a time-series of 2-D radiographs. This mapping, in turn, relates tothe neutron energy deposition in each region of tissue that the neutronstravelled through, and thus to the neutron dose. Discovery of neutrondose hotspots can be utilized as a guidance in subsequent treatments ofwhich tissue regions to avoid or minimize neutron dose exposure in orderto minimize secondary cancer risk.

With reference again to FIGS. 2 and 3, the processor 125 and memorydevice 126 of the imaging systems 120 and 130 are used to perform one ormore image processing algorithms that process the images captured by theradiation imager 106 to obtain certain useful information, such as, forexample, dose delivered to the target region and/or dose delivered toareas adjacent to the target region. The processor 125 may also performone or more algorithms that control the timing of image capture by theradiation imager 106 as well as motion of the arm 107 (FIG. 1) in caseswhere the arm is non-stationary. The processor 125 may also controlscanning of the charged particle beam produced by the source 101 incases in which the charged particle beam is scanned.

For example, because neutron images, which are also referred to hereinas radiographic images, are generated using the exit neutrons and/orphotons passing through the body of the patient 104, the resultingimages may be processed and analyzed by the processor 125 to assess thedose to anatomical structures adjacent to the target region. Theradiographic images provide a beam's eye view of regions that the protonbeam is incident on, and therefore provide geometrical verification ofthe proton beam. From this information, known calculations can be usedto determine the radiation dose to which the target region and adjacentregions are being exposed. Furthermore, consecutively captured 2-Dradiographic images can be analyzed to determine changes in the imagesover time. Such changes may be caused by patient movement or changes tosystem parameters, which should not occur but sometimes do. Based onthese determinations, the PT session can be modified, corrected orrepeated to improve treatment. Additionally, the radiographic images ofthe patient may be captured in different orientations to reconstruct athree-dimensional (3-D) image by, for example, imparting motion to thearm 127 in a predetermined manner while controlling the timing of imagecapture by the radiation imager 106 in a predetermined manner. Knownreconstruction algorithms can be used or adapted to reconstruct the 3-Dimages, as will be understood by those of skill in the art in view ofthe description provided herein.

2-D radiographs can be summed based on the radiation delivered over theentire duration of the proton beam delivery or they can be individualconsecutive serial radiographs, each based on delivery of a portion ofthe proton beam dose. As indicated above, these consecutive serialradiographs can be used to monitor changes in regions of the bodythrough which the proton beam passes. The consecutive serial radiographscan be acquired automatically by programming the optical sensor 114 tocapture the images in sequence or by programming the processor 125 tocontrol image capture by the optical sensor 114. In either case, it isunnecessary to pause the beam delivery. Hence a series of 2-Dradiographs, differing in time of collection, can be acquired during thebeam delivery.

When the imaging system 120 is used in conjunction with a scanningproton beam, it will yield a 2-D radiograph for each axial layer themonoenergetic proton beam stops within and deposits most of its energy.Each layer is associated with a different proton energy, and a treatmentbeam consists of a range of proton energies that are customized for eachpatient treatment based on the specific dose distribution required. Bycombining the 2-D radiographs for each layer, and knowing the protonbeam energy used to generate each layer, one can generate a 3-D image ofthe region of the patient volume irradiated by the proton beam. Thisvolume includes some or all of the SOBP region of the proton beam. This3-D image can be used to verify the intended delivery of the radiationby comparing this imaging with the treatment planning imaging andradiation dose distribution. In both cases, besides verifying that theproton beam is delivered within the intended patient volume, the imagingcan also be carried out on phantoms separately from treatment. In thelatter case, adjustments may be made to the treatment plan based on theradiographs that were captured for the phantom.

Furthermore, the radiographs captured by the imaging system 120 can beused to obtain a measure of the spatio-spectral distributions of theforward momentum neutrons, which may be used to optimize the dynamicenergy of the optical sensor 114 and to provide additional doseinformation on secondary neutron-induced cancer risk through neutronimaging using the imaging system 120, which directly related to neutronsgenerated, their origin and energy distribution, which are all theparameters determining specific neutron dose impact of various patientorgans during treatment.

Also, since the neutrons generated will be highly dependent not only onwhat the characteristics of a specific PT facility are, but also onwhich type of cancer is being treated and where it is located, theimages will allow for significant improvements in patient-by-patientimpact and risk. PPI can be used to verify geometric accuracy of theproton beam delivery. This imaging combined with measurements of theneutron spectrum can be used to estimate neutron dose within thepatient. The continuous imaging will allow for rapid identification ofpatient treatment irregularities which would be obtained by the imagingsystem 120, or post-treatment analysis and corrective action guidance ofsubsequent treatment for the same patient/tumor.

FIGS. 6A and 6B are graphs of the neutron spectral distributions thatwere measured using a He-4 gas detector at different angular locationsrelative to a water equivalent phantom that was irradiated using a beamof protons with an average energy of 176 MeV. The results of themeasurements indicate the suitability of these detectors for neutrondose verification. FIG. 6A shows the neutron differentiation ability(Pulse Shape discrimination (PSD)) of the proposed system utilizing He-4noble gas neutron detectors at a PT facility. The radiation environmentat a proton irradiation facility is high in dose and of mixed radiationcharacter. The PSD is performed on a pulse-by-pulse basis either inreal-time or as post-processing, utilizing pulse integral ratiocomparison of prompt and delayed scintillation pulse components inducedby neutrons and gamma-rays, respectively. The ability to separate theneutron pulses as shown here over a wide range of energies is essentialto proper neutron dose risk evaluation.

FIG. 6B shows the spectroscopic comparison of proton therapy institute(PTI) data (plot 161) with data from other known neutron sources, suchas deuterium-deuterium fusion-based neutron generator creating 2.45 MeVneutrons (DD, plot 162), and Californium-252 spontaneous fission sourcegenerating neutrons of a wide spectra with average energy 2 MeV (Cf-252,plot 163). The He-4 detector data demonstrates the wide range ofdetectable neutron energies. When taking into account theenergy-dependent neutron dose quality-factors, a direct neutronspectral-dependent detector response of neutron spectra is essential forcorrect patient-organ neutron-dose estimation. The neutron flux ismeasured after transport through the patient body, for a scanningparticle beam the sequence in time of patient-transmitted neutronspectra obtained in time enable dose calculation of forward affectedorgans and tissue. For a shaped beam, the same dose calculation wouldneed to utilize the patient-specific phantom that was used to alsogenerate the beam-profile and treatment plan, to obtain the correct doseto the target region and areas adjacent to the target region.

FIG. 7 is a flow diagram of the PPI method in accordance with arepresentative embodiment. A charged particle beam source generates acharged particle beam that is directed toward a target region of a bodyof a patient during a PT session such that an SOBP is produced inside ofthe patient's body that produces one or more of exit neutrons, forwardmomentum neutrons and photons, as indicated by block 171. With aradiation imager of an imaging system of the PPI system, at least aportion of the exit neutrons, forward momentum neutrons and/or photonsare received and one or more radiographic images are generated from theexit neutrons, forward momentum neutrons and/or photons, as indicated byblock 172. With a processor of the imaging system, one or moreradiographic images are received and one or more image processingalgorithms are performed that process the one or more radiographicimages to obtain information about the PT session, as indicated by block173.

FIG. 8 is a flow diagram representing the PPI method in accordance withone representative embodiment in which the processor 125 performs aparticular image processing algorithm to determine whether the positionof the patient has changed during the PT session. In accordance withthis representative embodiment, the radiation imager generates a seriesof radiographic images, where each radiographic image of the series iscaptured at a different instant in time during the PT session, asindicated by block 181. The image processing algorithm performed by theprocessor 125 analyzes the radiographic images of the series to identifyat least one particular feature that is present in each radiographicimage of the series, as indicated by block 182. Known featurerecognition algorithms may be used for this purpose. Once the particularfeature has been identified, the position of the feature within eachradiographic image can be used to determine whether the position of thefeature has changed over the different instants in time, as indicated byblock 183. If a determination is made that the position of theparticular feature has changed over time, then this is an indicationthat the patient's position has likely changed, which may be anindication that the PT session should be repeated or that some changeshould be made to the treatment plan.

FIG. 9 is a flow diagram representing the PPI method in accordance withanother representative embodiment in which the processor 125 performs aparticular image processing algorithm that verifies whether or not thegeometry of the charged particle beam at the target region during the PTsession is in accordance with the treatment plan. As indicated above,one image processing algorithm that can be performed by the processoranalyzes one or more radiographic images to verify that the geometry ofthe charged particle beam at the target region during the PT session isin accordance with the treatment plan. In FIG. 9, blocks 191 and 192 areidentical to blocks 171 and 172, respectively, shown in FIG. 7. At block193, the processor analyzes one or more radiographic images to verifythat the geometry of the charged particle beam at the target regionduring the PT session is in accordance with the treatment plan. Inaccordance with this embodiment, the radiographic images can be 2-D or3-D radiographic images.

FIG. 10 is a flow diagram representing the PPI method in accordance withanother representative embodiment in which the processor 125 performs aparticular image processing algorithm that analyzes one or moreradiographic images to determine the radiation dose of the chargedparticle beam delivered at the target region during the PT session. Asindicated above, one image processing algorithm that can be performed bythe processor 125 analyzes one or more radiographic images to determinethe radiation dose of the charged particle beam delivered at the targetregion during the PT session. This can be compared with the treatmentplan to determine whether the dose delivered to the target region was isin accordance with the treatment plan. In FIG. 10, blocks 201 and 202are identical to blocks 171 and 172, respectively, shown in FIG. 7.Block 203 represents the step of the processor analyzing one or moreradiographic images to determine the radiation dose of the chargedparticle beam delivered at the target region during the PT session.

FIG. 11 is a flow diagram representing the PPI method in accordance withanother representative embodiment in which the processor 125 performs aparticular image processing algorithm that analyzes one or moreradiographic images to determine the radiation dose of the chargedparticle beam delivered to areas adjacent to the target region duringthe PT session. As indicated above, at least one image processingalgorithm performed by the processor can analyze one or moreradiographic images to determine the radiation dose of the chargedparticle beam delivered to areas adjacent to the target region duringthe PT session. This can be compared with the treatment plan todetermine whether to dose delivered to adjacent areas is in accordancewith the treatment plan. In FIG. 11, blocks 211 and 212 are identical toblocks 171 and 172, respectively, shown in FIG. 7. Block 213 representsthe step of the processor 125 analyzing one or more radiographic imagesto determine the radiation dose of the charged particle beam deliveredto areas adjacent to the target region during the PT session.

FIG. 12 is a flow diagram representing the PPI method in accordance withanother representative embodiment in which the processor 125 performs aparticular image processing algorithm that reconstructs a 3-Dradiographic image from a plurality of 2-D radiographic images capturedat different angular positions of the radiation imager 106. A chargedparticle beam source generates a charged particle beam that is directedtoward a target region of a body of a patient during a PT session suchthat an SOBP is produced inside of the patient's body that produces oneor more of exit neutrons, forward momentum neutrons and photons, asindicated by block 221. With a radiation imager of an imaging system ofthe PPI system, at least a portion of the exit neutrons, forwardmomentum neutrons and/or photons are received and at least one 2-Dradiographic image is generated from the exit neutrons, forward momentumneutrons and/or photons, as indicated by block 222. Block 223 representsthe step of determining whether a 2-D radiographic image has beencaptured by the radiation imager at each angular position. If not, theangular position of the radiation imager is changed, as indicated byblock 224, and the process returns to block 222 where the next 2-Dradiographic image is generated at the new angular position. Once animage has been captured at each angular position, as determined at block223, the process proceeds to block 225 at which the processor 125performs a reconstruction algorithm that reconstructs a 3-D radiographicimage from the plurality of 2-D radiographic images.

FIG. 13 is a flow diagram representing the PPI method in accordance withanother representative embodiment in which the processor 125 performs aparticular image processing algorithm that generates a 2-D radiographicimage for each layer of the target region while the charged particlebeam is scanned layer by layer and then combines the 2-D radiographs forall of the scanned layers based on the charged beam energy associatedwith each scanned layer to generate a 3-D radiographic image of thetarget region. At block 231, the scanning charged particle beam sourcegenerates a charged particle beam that is directed toward a targetregion of a body of a patient during a PT session such that an SOBP isproduced inside of the patient's body that produces one or more of exitneutrons, forward momentum neutrons and photons, as indicated by block231. With the radiation imager, for each scanned layer, at least aportion of the exit neutrons, forward momentum neutrons and/or photonsare received and at least one 2-D radiographic image is generated fromthe exit neutrons, forward momentum neutrons and/or photons, asindicated by block 232. Block 233 represents the step of determiningwhether a 2-D radiographic image has been captured by the radiationimager for each scanned layer. If not, the charged particle beamposition is changed, as indicated by block 234, and the process returnsto block 231. Once a 2-D radiographic image has been generated for eachlayer of the target region, as determined at block 233, the processproceeds to block 235 at which the processor 125 performs areconstruction algorithm that reconstructs a 3-D radiographic image bycombining the plurality of 2-D radiographic images based on the beamenergy associated with each respective scanned layer.

FIG. 14 is a flow diagram representing the PPI method in accordance withanother representative embodiment in which the processor 125 performs aparticular image processing algorithm that determines, based on the 3-Dradiographic image, whether a radiation dose delivered by the chargedparticle beam to the target region during the PT session met constraintsof a treatment plan for an intended radiation dose to be deliveredduring the PT session. The process shown in FIG. 14 can begin fromblocks 225 or 235 shown in FIGS. 12 and 13, respectively. Block 241shown in FIG. 14 represents the step of the processor 125 performing aparticular image processing algorithm that determines, based on the 3-Dradiographic image, whether the radiation dose delivered by the chargedparticle beam to the target region during the PT session met constraintsof a treatment plan for an intended radiation dose to be deliveredduring the PT session.

FIG. 15 is a flow diagram representing the PPI method in accordance withanother representative embodiment in which the processor 125 performs aparticular image processing algorithm that determines, based on the 3-Dradiographic image, whether a radiation dose delivered by the chargedparticle beam to areas adjacent to the target region during the PTsession met constraints of a treatment plan. The process shown in FIG.15 can begin from blocks 225 or 235 shown in FIGS. 12 and 13,respectively. Block 251 shown in FIG. 15 represents the step of theprocessor 125 performing a particular image processing algorithm thatdetermines, based on the 3-D radiographic image, whether the radiationdose delivered by the charged particle beam to adjacent areas to thetarget region during the PT session met constraints of a treatment plan.

In accordance with a representative embodiment the processor 125performs a particular image processing algorithm that determines, basedon the outcome of one or more of the processes depicted in FIGS. 7-15,whether constraints of a treatment plan are being met during the PTsession (if performed in real-time) or whether the constraints were metif the determination is made offline, i.e., after the PT session hasbeen performed.

It should be noted that the algorithms that are performed by theprocessor 125, such as the image processing algorithms described above,for example, are typically performed in software or firmware that isexecuted by the processor 125. Such software and/or firmware may bestored in a non-transitory computer-readable medium, such as memorydevice 126. Some embodiments can be implemented in hardware or in acombination of hardware and software and/or firmware. If implemented inhardware, as in an alternative embodiment, the processor 125 can beimplemented with any or a combination of the following technologies,which are all well known in the art: a discrete logic circuit(s) havinglogic gates for implementing logic functions upon data signals, anapplication specific integrated circuit (ASIC) having appropriatecombinational logic gates, a programmable gate array(s) (PGA), a fieldprogrammable gate array (FPGA), etc.

It should be emphasized that the above-described embodiments are merelypossible examples of implementations for the purposes of providing aclear understanding of the inventive principles and concepts. Manyvariations and modifications may be made to the above-describedembodiments without departing from the scope of the inventive principlesand concepts. All such modifications and variations are intended to beincluded herein within the scope of this disclosure and the presentinvention and protected by the following claims.

What is claimed is:
 1. A particle portal imaging (PPI) systemcomprising: a charged particle beam source that generates a chargedparticle beam that is directed toward a target region of a body of apatient such that a spread out bragg peak (SOBP) is produced inside ofthe patient's body, the SOBP inside of the body producing at least exitneutrons; and an imaging system comprising: a radiation imagerpositioned to receive at least a portion of the exit neutrons and togenerate one or more radiographic images from said at least a portion ofthe exit neutrons; and a processor in communication with the radiationimager to receive said one or more radiographic images, the processorbeing configured to perform one or more image processing algorithms thatprocess said one or more radiographic images to obtain information aboutthe patient.
 2. The PPI system of claim 1, wherein the radiation imageris configured to perform a preferential selection process that selectsthe exit neutrons that are used to generate said one or moreradiographic images based at least in part on energy levels of the exitneutrons.
 3. The PPI system of claim 1, wherein the radiation imagercomprises: a converter that receives said at least a portion of the exitneutrons and converts said at least a portion of the exit neutrons intolight propagating in a first direction; a mirror that receives the lightpropagating in the first direction and directs at least a portion of thereceived light into light propagating in a second direction that is at anon-zero-degree angle to the first direction; and an optical sensor thatreceives at least a portion of the light propagating in the seconddirection, the optical sensor comprising an array of sensor elements,each sensor element generating a respective electrical signal based onan amount of the light received thereby, each radiographic imagecorresponding to a combination of the electrical signals generated bythe sensor elements at a given time instant.
 4. The PPI system of claim3, wherein the converter is a scintillator.
 5. The PPI system of claim3, wherein the mirror is a forty-five-degree mirror, and wherein thesecond direction is at a forty-five-degree angle to the first direction.6. The PPI system of claim 3, wherein the optical sensor is a chargecoupled device (CCD) sensor.
 7. The PPI system of claim 3, wherein theoptical sensor is a complementary metal oxide semiconductor (CMOS)sensor.
 8. The PPI system of claim 1, wherein the radiation imagercomprises: a detector that receives said at least a portion of the exitneutrons and converts said at least a portion of the exit neutrons intosaid one or more radiographic images.
 9. The PPI system of claim 1,wherein the charged beam source is a proton beam source that generates aproton beam.
 10. The PPI system of claim 1, wherein the radiation imagergenerates a series of radiographic images, each radiographic image ofthe series being captured at a different instant in time during the PTsession, and wherein at least one of the image processing algorithmsperformed by the processor analyzes the radiographic images of theseries to identify at least one particular feature that is present ineach radiographic image of the series and to determine whether aposition of the particular feature has changed over the differentinstants of time.
 11. The PPI system of claim 1, wherein at least oneimage processing algorithm performed by the processor analyzes said oneor more radiographic images to verify a geometry of the charged particlebeam at the target region during a charged particle treatment (PT)session.
 12. The PPI system of claim 1, wherein at least one imageprocessing algorithm performed by the processor analyzes said one ormore radiographic images to determine a radiation dose of the chargedparticle beam delivered to the target region during a charged particletreatment (PT) session.
 13. The PPI system of claim 1, wherein at leastone image processing algorithm performed by the processor analyzes saidone or more radiographic images to determine a radiation dose of thecharged particle beam delivered to areas adjacent to the target regionduring a charged particle treatment (PT) session.
 14. The PPI system ofclaim 1, wherein the radiation imager is moved relative to the patientduring the PT session to change an angle of the radiation imagerrelative to the charged particle beam, and wherein a plurality oftwo-dimensional (2-D) radiographic images are captured by the radiationimager at different respective angles of the radiation imager relativeto the charged particle beam, and wherein at least one image processingalgorithm performed by the processor is a reconstruction algorithm thatgenerates one or more three-dimensional (3-D) radiographic images fromthe 2-D radiographic images.
 15. The PPI system of claim 1, wherein thecharged particle beam comprises a pencil beam that is scanned throughlayers of the body of the patient during the PT session such that atleast one two-dimensional (2-D) radiographic image is generated by theradiation imager per scanned layer, and wherein one image processingalgorithm performed by the processor combines the 2-D radiographs forall of the scanned layers and uses a proton beam energy associated witheach scanned layer to generate a three-dimensional (3-D) radiographicimage of the target region.
 16. The PPI system of claim 15, wherein oneimage processing algorithm performed by the processor determines, basedon the 3-D radiographic image, whether or not actual delivery of thecharged particle beam to the target region met constraints of atreatment plan for an intended delivery of the charged particle beam tothe target region.
 17. The PPI system of claim 16, wherein one imageprocessing algorithm performed by the processor determines, based on the3-D radiographic image, whether a radiation dose delivered by thecharged particle beam to the target region met constraints of atreatment plan for an intended radiation dose to be delivered during acharged particle treatment (PT) session.
 18. The PPI system of claim 17,wherein one image processing algorithm performed by the processormodifies, based on the 3-D radiographic image, a treatment planassociated with the patient.
 19. A method for performing particle portalimaging (PPI) comprising: with a charged particle beam source of a PPIsystem, generating a charged particle beam and directing the chargedparticle beam toward a target region of a body of a patient such that aspread out bragg peak (SOBP) is produced inside of the patient's body,the SOBP inside of the body producing at least exit neutrons; with aradiation imager of an imaging system of the PPI system, receiving atleast a portion of the exit neutrons and generating one or moreradiographic images from said at least a portion of the exit neutrons;and with a processor of the imaging system, receiving said one or moreradiographic images and performing one or more image processingalgorithms that process said one or more radiographic images to obtaininformation about the patient.
 20. The method of claim 19, furthercomprising: in the radiation imager, performing a preferential selectionprocess that selects the exit neutrons that are used to generate saidone or more radiographic images based at least in part on the energylevels of the exit neutrons.